The overarching aim of this proposed project is to develop, optimize and quantitatively evaluate magnetic resonance imaging (MRI) methods for evaluating the biomechanical properties of bone. The current standard diagnostic of bone health, dual-energy X-ray absorptiometry (DXA), provides an approximate measure of bone mineral density, but it is a projection method that does not incorporate the full contribution of macro-structure, micro-architecture, collagen, or porosity to fracture resistance. Quantitative computed tomography (qCT) is able to partially circumvent these shortcomings of DXA, but remains limited in that it, and other X-ray based methods, are sensitive only to the mineral content of bone, which accounts for only ~~40% of bone by volume. Recent studies have shown that [1]H nuclear magnetic resonance (NMR) can discern multiple soft- tissue components of bone, including collagen, collagen-bound water, and pore water. Further, in cadaveric cortical bone samples, these NMR measures were found to better predict several mechanical properties related to bone fracture risk than current high resolution qCT. This project seeks to translate these [1]H NMR findings into clinical MRI methods for assessing whole bone fracture risk through three project aims.
In Aim 1, [1]H NMR measurements from cortical bone samples will be used to design and test MRI methods for quantitatively measuring bound- and pore-water from bone.
In Aim 2, these MRI methods, along with DXA and qCT, will be applied to multiple cadaveric bone sites (including the femoral neck and distal radius). The resulting MRI measures of bound-water, pore-water, and cross-sectional moment of inertia will be correlated with whole bone fracture resistance properties measured from the same sites and a lumbar vertebra. Similar correlations will be made between DXA and qCT measures for comparison.
In Aim 3, the MRI methods will be translated to a human MRI system where they will be re-optimized for 3T (c/w 4.7T) and quantitatively evaluated for use at multiple anatomical sites (e.g., distal tibia femoral neck, ...). Ultimately, this project will result in MRI methods with the potential for improved clinical diagnostic evaluation of fracture risk and novel imaging biomarkers for the study bone disease and pharmacological treatment response.

Public Health Relevance

Current methods for diagnostic imaging of bone are incomplete and do not fully predict the increase in fracture risk with age or advancement of disease (such as osteoporosis). Unlike current X-ray based imaging, MRI can probe soft-tissue characteristics of bone, which may be important in fracture resistance. The proposed research aims to develop and evaluate MRI methods that can beDer predict bone fracture risk and provide more specific feedback on bone composition changes in response to therapy.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Research Project (R01)
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Medical Imaging Study Section (MEDI)
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Liu, Guoying
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Vanderbilt University Medical Center
Schools of Medicine
United States
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Manhard, Mary Kate; Nyman, Jeffry S; Does, Mark D (2017) Advances in imaging approaches to fracture risk evaluation. Transl Res 181:1-14
Uppuganti, Sasidhar; Granke, Mathilde; Manhard, Mary Kate et al. (2017) Differences in sensitivity to microstructure between cyclic- and impact-based microindentation of human cortical bone. J Orthop Res 35:1442-1452
Manhard, Mary Kate; Harkins, Kevin D; Gochberg, Daniel F et al. (2017) 30-Second bound and pore water concentration mapping of cortical bone using 2D UTE with optimized half-pulses. Magn Reson Med 77:945-950
Uppuganti, Sasidhar; Granke, Mathilde; Makowski, Alexander J et al. (2016) Age-related changes in the fracture resistance of male Fischer F344 rat bone. Bone 83:220-232
Manhard, Mary Kate; Uppuganti, Sasidhar; Granke, Mathilde et al. (2016) MRI-derived bound and pore water concentrations as predictors of fracture resistance. Bone 87:1-10
Granke, Mathilde; Makowski, Alexander J; Uppuganti, Sasidhar et al. (2015) Identifying Novel Clinical Surrogates to Assess Human Bone Fracture Toughness. J Bone Miner Res 30:1290-300
Li, Ke; Dortch, Richard D; Kroop, Susan F et al. (2015) A rapid approach for quantitative magnetization transfer imaging in thigh muscles using the pulsed saturation method. Magn Reson Imaging 33:709-17
Manhard, Mary Kate; Horch, R Adam; Gochberg, Daniel F et al. (2015) In Vivo Quantitative MR Imaging of Bound and Pore Water in Cortical Bone. Radiology 277:221-9
Granke, Mathilde; Does, Mark D; Nyman, Jeffry S (2015) The Role of Water Compartments in the Material Properties of Cortical Bone. Calcif Tissue Int 97:292-307
Harkins, Kevin D; Horch, R Adam; Does, Mark D (2015) Simple and robust saturation-based slice selection for ultrashort echo time MRI. Magn Reson Med 73:2204-11

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